Contribution of Endothelin-1 to Exercise Intolerance in Heart Failure

NCT02124824 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: F1418-P
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Heart disease is the leading cause of death in the United States, accounting for one in every four deaths in 2010 and costing over $300 billion annually in health care, medication, and lost productivity. Heart failure (HF), a clinical syndrome that develops as a consequence of heart disease, is characterized by the worsening of symptoms, such as dyspnea and fatigue, upon exertion, collectively defined as "exercise intolerance". Surprisingly, exercise intolerance does not correlate with the degree of cardiac contractile (ventricular) dysfunction, suggesting that changes in the peripheral circulation may be to blame for exercise intolerance in this cohort. Though there are a host of factors that may contribute to this impairment, disease-related increases in circulating endothelin-1 (ET-1) may be a significant factor in the sequelae of exercise intolerance in HF. Thus, the overall purpose of this Small Projects in Rehabilitation Research (SPiRE) proposal is to explore the contribution of ET-1 to chronic vasoconstriction in HF patients, and to examine whether inhibition of this pathway could improve vasodilatory ability, and thus exercise tolerance, in Veterans with HF.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Blood Flow

  Ultrasound Doppler

  two years

Study Arms (2)

Arm 1: Control

EXPERIMENTAL

Control

Drug: BQ-123

Arm 2: Heart Failure

EXPERIMENTAL

Heart Failure

Drug: BQ-123

Interventions

BQ-123 DRUG

Endothelin subtype A antagonist

Arm 1: Control; Arm 2: Heart Failure

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• The study group will include subjects with a history of stable cardiomyopathy (ischemic and non-ischemic, \>3 months duration, ages 45-75 yrs) despite a minimum of 6 weeks of optimal treatment.
• Optimal therapy will be according to AHA/ACC and HFSA HF guidelines, including treatment with ACE and -blocker therapy (for at least 6 weeks), or have documented reason for variation, including medication intolerance, contraindication, patient preference, or personal physician's judgment.
• Patient enrollment will be limited to those individuals with NYHA class II and III symptoms, LVEF\<35%, with no or minimal smoking history (\<15 pk yrs), and without pacemakers.
• Patients with atrial fibrillation or HF believed to be secondary to atrial fibrillation will be excluded.
• Patients with HF secondary to significant uncorrected primary valvular disease (except mitral regurgitation secondary to left ventricular dysfunction) will also be excluded.
• Patients will be sedentary, defined here as no regular physical activity for at least the prior 6 months and current activity level will be documented by an activity questionnaire.
• Patients must have no orthopedic limitations that would prohibit them from performing knee-extensor exercise.
• Due to the typical age of patients with HF, all women will be postmenopausal (either natural or surgical) defined as a cessation of menses for at least 2 years, and in women without a uterus, follicle stimulating hormone (FSH) \>40 IU/L.
• These include a diagnosis of Dementia
• Severe COPD
• Peripheral Vascular Disease
• Anemia
• Sleep-related Breathing Disorder
• Severe Valvular Heart Disease
• Diabetes (if on insulin therapy)

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of Utah: collaborator

Study Sites (1)

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

cyclo(Trp-Asp-Pro-Val-Leu)

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Scott Capps
• Organization: VAMC SLC

Scott.Capps@hsc.utah.edu

8015821565

Study Officials

• David W. Wray, PhD

  VA Salt Lake City Health Care System, Salt Lake City, UT

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2014
• First Posted: April 28, 2014
• Study Start: September 1, 2014
• Primary Completion: March 31, 2019
• Study Completion: March 31, 2019
• Last Updated: December 20, 2021
• Results First Posted: December 20, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)